Rheumatoid arthritis is the most common autoimmune disease, affecting around 1 in 100 people. It causes painful and persistent swelling in the joints that can result in damage to the bone and cartilage.
Around half of all patients do not respond to one or more of the treatments currently available, and even these can become less successful over time. The researchers behind the new study say stopping the disease closer to the root of the problem could be the best way to treat it, and their results suggest a new target for therapies.
When a microbe infects the body, the body responds by turning on a molecular switch to set the immune system into action and protect the body from disease. Today's findings show that a signal molecule called tenascin-C can trigger the same molecular switch and also activate the immune system. High levels of tenascin-C present in joints therefore may cause the activated immune system to attack the joint leading to the persistent inflammation of rheumatoid arthritis.
The molecular switch is called TLR4, and is found on the surface of immune cells. Previous research has shown that mice without TLR4 do not show chronic joint inflammation. The researchers hope scientists can develop new treatments that target the interaction between tenascin-C and TLR4, which may help to combat rheumatoid arthritis.
Dr Kim Midwood, lead author of the study from the Kennedy Institute of Rheumatology at Imperial College London, said: "Rheumatoid arthritis is a debilitating and painful disease and, unfortunately, there is no cure. Furthermore, current treatments are not effective for many patients."
"We have uncovered one way that the immune system may be triggered to attack the joints in patients with rheumatoid arthritis. We hope our new findings can be used to develop new therapies that interfere with tenascin-C activation of the immune system and that these will reduce the painful inflammation that is a hallmark of this condition," added Dr Midwood.
The researchers reached their conclusions by carrying out five studies. One study suggested that tenascin-C was needed to sustain inflammation. The researchers induced joint inflammation in mice with and without the gene for tenascin-C. They found the mice that could produce tenascin-C had severe joint swelling with bone and cartilage destruction, but the mice that could not produce tenascin-C had no swelling or tissue destruction at all.
In a subsequent study, the researchers injected the active part of the tenascin-C molecule into mice joints. They found it caused the joints of the mice to become inflamed and that this reaction was more intense with higher doses.
Another experiment demonstrated that tenascin-C causes swelling in the joints by increasing levels of molecules that cause inflammation. The researchers took human immune cells called macrophages and cells called fibroblasts from the swollen joint of patients with rheumatoid arthritis and added tenascin-C. After the tenascin-C was added, the cells produced more molecules that cause inflammation.
The authors plan to work out the precise mechanism by which tenascin-C increases these levels of inflammatory molecules in the human joint and try to find ways to inhibit this action.
This work was funded by the Arthritis Research Campaign, The Kennedy Institute of Rheumatology Trustees and an MRC New Investigators Research Grant awarded to K. M. The researchers are also grateful for support from the NIHR Biomedical Research Centre funding scheme.
Lucy Goodchild | EurekAlert!
Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
Foods of the future
15.08.2018 | Georg-August-Universität Göttingen
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences